medwireNews: Radiotherapy (RT) is “essential” in first-line management of patients with early-stage natural killer/T-cell lymphoma (NKTCL), say researchers who found that the associated gain in locoregional control with the treatment translates to better survival.

“The optimal dose was 50 Gy for patients with early-stage disease”, the team reports in JAMA Oncology.

The review of data from 10 institutions in China included 1332 patients treated for NKTCL between 2000 and 2014 with chemotherapy followed by RT (n=653), RT followed by chemotherapy (n=215), RT alone (n=292) or chemotherapy alone (n=172).

The median radiation dose in patients given RT was 50 Gy; 86% of patients treated with RT received at least 50 Gy, 14% a dose of 10–49 Gy and 4% less than 40 Gy. Chemotherapy alone was considered to be a dose of 0 Gy for dose–effect analysis. Among the patients given chemotherapy, 80% received a doxorubicin-based regimen and the remainder L-asparaginase- or gemcitabine-based regimens.

Analysis demonstrated that the risk of the endpoints of locoregional recurrence, disease progression and mortality all “decreased sharply” as RT dose increased up to a dose 50–52 Gy, say Ye-Xiong Li, from the National Cancer Center in Beijing, China, and co-authors.

The improved locoregional recurrence rate with RT occurred regardless of the sequence of RT or chemotherapy, and independently of whether the patient initially responded to chemotherapy.

However, these two factors were significantly associated with survival endpoints in patients with high-risk early-stage disease, the researchers note. “This raises the possibility that [chemotherapy] improves survival by acting on distant micrometastatic disease more so than via local effects”, they comment.

Finally, dose–response regression analysis confirmed that there were significant, linear relationships between 5-year rates of locoregional recurrence and progression-free survival and overall survival. These results were externally validated using previously published locoregional recurrence and survival data, the team adds.

“In view of the recognized high cure rate of RT and evidence for a dose–response relationship, adherence to RT plays a greater role in both [locoregional control] and survival”, they conclude.

The authors add: “Clinical trials designed to define optimal therapies or novel [chemotherapy] regimens without inclusion of RT may not be acceptable or ethical in early-stage NKTCL. A combination of upfront, optimal RT and effective systemic therapy may provide the ideal spatial combination for first-line therapy in early-stage NKTCL.”